Anighoro Andrew, Bajorath Jürgen, Rastelli Giulio
Life Sciences Department, University of Modena and Reggio Emilia , Via Campi 183, 41125 Modena, Italy.
J Med Chem. 2014 Oct 9;57(19):7874-87. doi: 10.1021/jm5006463. Epub 2014 Jun 25.
At present, the legendary magic bullet, i.e., a drug with high potency and selectivity toward a specific biological target, shares the spotlight with an emerging and alternative polypharmacology approach. Polypharmacology suggests that more effective drugs can be developed by specifically modulating multiple targets. It is generally thought that complex diseases such as cancer and central nervous system diseases may require complex therapeutic approaches. In this respect, a drug that "hits" multiple sensitive nodes belonging to a network of interacting targets offers the potential for higher efficacy and may limit drawbacks generally arising from the use of a single-target drug or a combination of multiple drugs. In this review, we will compare advantages and disadvantages of multitarget versus combination therapies, discuss potential drug promiscuity arising from off-target effects, comment on drug repurposing, and introduce approaches to the computational design of multitarget drugs.
目前，传说中的神奇子弹，即对特定生物靶点具有高效力和选择性的药物，正与一种新兴的、替代性的多药理学方法共同成为焦点。多药理学表明，通过特异性调节多个靶点可以开发出更有效的药物。人们普遍认为，癌症和中枢神经系统疾病等复杂疾病可能需要复杂的治疗方法。在这方面，一种“击中”属于相互作用靶点网络的多个敏感节点的药物具有更高疗效的潜力，并且可能限制通常因使用单靶点药物或多种药物组合而产生的缺点。在本综述中，我们将比较多靶点疗法与联合疗法的优缺点，讨论由脱靶效应引起的潜在药物混杂性，评论药物再利用，并介绍多靶点药物的计算设计方法。
